Despite the long and established history of antibiotic therapy, bacterial infections remain a major health concern for both industrialized and third world countries. Some of this concern stems from the growing number of antibiotic resistant organisms, which the U.S. Centers for Disease Control and Prevention estimates to be responsible for over 2 million infections and 23,000 deaths in the U.S. annually. For example, one of the most common infections caused by these pathogens is pneumonia, which is often associated with high morbidity and mortality.
Some of the bacterial pathogens that are of particular concern include multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus. These antibiotic resistant organisms generally limit the efficacy of existing antibiotic therapy and make treatment of the resulting infection difficult, if not impossible. Additionally, various other pathogens, such as isolates of Acinetobacter baumannii, have developed resistance to all available antibiotics, which has led to the concern that traditional antibiotic therapy will soon become obsolete.
A. baumannii is an important nosocomial pathogen that persists on abiotic surfaces and causes a range of infections, including respiratory and urinary tract infections, meningitis, endocarditis, bloodstream infections, burn infections, wound infections, and bacteremia. A. baumannii accounts for 1% of all hospital-acquired blood stream infections making it one of the ten most frequent causes of this type of pathology (Wisplinghoff et al., 2004; Gales et al., 2001). In addition, A. baumannii accounts for 3% of all pneumonia cases in coronary care units, and 15-25% of ventilator-associated pneumonias are attributable to this pathogen (Gales et al., 2001; Knapp et al., 2006). In total, A. baumannii is responsible for approximately 10% of total intensive care unit (ICU) infections worldwide (Vincent et al., 2009). Indeed, pneumonia due to A. baumannii is one of the most difficult hospital-acquired infections to control and treat (Vincent et al., 2009), and this is underscored by the fact that ventilator-associated pneumonias caused by A. baumannii infections have a crude mortality rate that can approach 75% (Chastre and Trouillet, 2000).
The importance of A. baumannii as an emerging cause of infection is also notable in the Armed Forces. The significance of A. baumannii to the health of combat soldiers was first recognized during the Vietnam War, where A. baumannii was reported to be the most common Gram negative bacillus recovered from traumatic injuries to extremities. More recently, drug-resistant A. baumannii has become an increasing problem in soldiers wounded in Iraq and Afghanistan. In fact, A. baumannii is now recognized as one of the most significant infectious threats to soldiers wounded in combat, placing a considerable burden on the health of our Armed Forces (Abbott, 2005; Morb. Mortal Wkly Rep. (MMWR), 2004).
Despite these serious medical concerns, however, the significance of A. baumannii in developed countries is dwarfed by the impact of this organism on the developing world. In Africa and Asia, A. baumannii is responsible for approximately 15-20% of all ICU infections, representing a considerable public health challenge (Vincent et al., 2009). A. baumannii has also established itself as a predominant cause of serious neonatal infections in the Indian subcontinent (Srivastava and Shetty, 2007). The incidence rate of Acinetobacter septicaemia in India is as high as 11.1 per 1000 live births and Acinetobacter associated with surgical infections in South African children can lead to a 100% mortality rate (Jeena et al., 2001). In addition to hospital-acquired infections, community-acquired pneumonia due to A. baumannii has been described for tropical regions of Australia and Asia with a mortality rate of 40-60% (Leung et al., 2006).
A. baumannii is also a leading cause of infection following natural disasters. A. baumannii was the leading cause of infection following the 2008 earthquake in Wenchuan, China and the Marmara earthquake in northwestern Turkey (Oncul et al., 1999). Additionally, A. baumannii was a primary cause of infection in survivors of the Indonesian tsunami of 2004 (Maegele et al., 2005).
The clinical significance of A. baumannii has been propelled by this organism's rapid acquisition of resistance to virtually all antibiotics. In many cases, the only remaining effective antimicrobial agent for treatment of A. baumannii infections is colistin (polymyxin E); however, this agent is seldom used because of its high toxicity. Isolates of A. baumannii that are resistant to all known antibiotics have recently emerged, representing a sentinel event signalling the end of the antibiotic era. Clearly, this organism threatens the utility of our current antibacterial armamentarium. It is for these reasons that the Infectious Diseases Society of America in its Bad Bugs No Drugs campaign has recommended that significant resources be devoted to developing novel antimicrobials against A. baumannii. (Talbot et al., 2006; Peleg et al., 2008). However, despite the recommendation that significant resources be devoted, new compositions and methods for treating Acinetobacter baumannii infections, as well as other bacterial infections, have yet to be developed that effectively avoid the issues associated with antibiotic resistance.